Inhibitors against glycosyltransferases and glycosidases, which build up oligosaccharide moieties of biologically active glycoconjugates, are essential tools for the development of glycobiology and promising candidates of novel agents for the treatments of tumors, inflammatory, autoimmune diseases, and bacterial and virus infections. Many excellent inhibitors against glycosidases, such as deoxynojirimycin and oseltamivir, were found from nature and developed by good combination of structural biology and synthetic chemistry. However, excellent inhibitors of glycosyltransferases have not been developed until recently, because of little information on the structures of active sites of the enzymes, involvement of several components in the transition state of the enzyme catalyzed reaction, low affinities between the enzymes and substrates, and no facile assay systems for the inhibitory activities. The strategies regarding the design and the synthesis of the inhibitors for glycosyltransferases have been remarkably advanced in the last five years. In this review, we summarize the current stage of the synthesis of inhibitors against glycosyltransferases.
Transition metal-catalyzed cycloaddition is an atom-economical and powerful synthetic tool for the construction of cyclic carbon skeletons. Various types of cycloadditions, including [2 + 2 + 1], [2 + 2 + 2], [4 + 2] cycloaddition, etc., have been reported. Their asymmetric versions using chiral transition metal catalysts have also been reported to give enantiomerically-enriched multi-cyclic compounds. First, an iridium-catalyzed enantioselective Pauson-Khand-type reaction is summarized. Pauson-Khand (-type) reaction is a [2 + 2 + 1] cycloaddition of an alkyne, alkene and carbon monoxide, and gives synthetically useful cyclopentenones. Rhodium- and iridium-catalyzed Pauson-Khand-type reactions using an aldehyde as a CO source were also mentioned. Second, two types of enantioselective [2 + 2 + 2] cycloadditions are described : One is an iridium-catalyzed [2 + 2 + 2] cycloaddition of diynes and monoalkynes for the synthesis of chiral teraryls with two axial chiralities. Another is a rhodium-catalyzed [2 + 2 + 2] cycloaddition of enynes and monoalkynes for the synthesis of bicyclic cyclohexa-1, 3-dienes with a chiral quaternary carbon center. Third, a rhodium-catalyzed enantioselective [2 + 2] cycloaddition of alkynes and alkenes for the synthesis of chiral cyclobutenes is mentioned.
Prostacyclin (PGI2) is primarily secreted from vascular endothelium and plays an extremely important inhibitory role in platelet aggregation and as a vasodilator in maintaining homeostatic circulation. Despite fascinating pharmacological properties, the inherent instability and side effect of prostacyclin limit its therapeutic applicability. In this paper, we described that discovery of three classes of prostacyclin mimetics without PG skeleton, which are cycloalkene skeleton type (FR 181560, FR 181157), tetrahydronaphthalene skeleton type (FK 788), and amino acid type (FR 193264, FR 193262). Several designed prostacyclin mimetics exhibited potent PGI2 agonistic activity with good selectivity for IP receptor and bioavailability. The specific compounds were prepared by asymmetric synthesis with high selectivity. Furthermore, we also described metabolism study using rat and human liver microsomes to lead new drug design (FR 223346, FR 232149).
This article reports new ring-opening reactions of oxetane compounds with certain reagents such as acyl chlorides, carboxylic esters, phenols, and carboxylic acids using certain quaternary onium salts as catalysts. Reaction behavior of oxetanes was investigated based on kinetic study. These new reactions of oxetanes were also successfully applied to polymer synthesis. Polymers containing pendant reactive groups were obtained by polyaddition of bis (oxetane) s with certain difunctional monomers such as dicarboxylic chlorides, bis (phenol) s, or dicarboxylic acids. The reaction of oxetanes with cyclic carboxylic anhydrides proceeded in alternating ring-opening copolymerization mode to give copolymers with A-B sequence. The authors found new anionic ring-opening polymerization of oxetanes containing pendant hydroxyl groups using appropriate catalyst system. Hyperbranched polymers containing hydroxyl groups were prepared by the reactions of oxetanes. Alkali developable photopolymers were also obtained by the chemical modification of the hyperbranched polymers. The reactions of oxetanes with certain reagents were also useful for thermal curing reaction providing oxetane resins.
The helical structure is one of the most significant motifs in macromolecules. In nature, helical structures are often found in biomacromolecules, and they appear to play a critical role in biological phenomena such as molecular recognition and information storage, as exemplified by the double helices of DNA and the α-helix of proteins. Some synthetic polymers and oligomers also adopt a helical conformation. Recently, the design and synthesis of macromolecules with a helical structure has attracted a great deal of interest, in view of their relationship to life science, as well as of their potential applications in materials science. This review deals mainly with 1) foldamers, 2) foldamer as receptors, and 3) helical folding in the cavity of helical polymers. The foldamer is any oligomer that folds into a conformationally ordered state in solution, the structure of which is stabilized by a collection of noncovalent interactions between nonadjacent monomer units. Recently, a number of examples of foldamers such as oligo (aromatic amide) and oligo (m-pheny-lene-ethynylene) have been reported. The foldamers can be employed as receptors for small molecules and metal ions confined within the helical cavity. The helical folding of oligomers in the cavity of helical polymers is also described.
Introduction of four aryl groups on the highly reactive o-quinodimethane (o-QDM) skeleton suppresses the intermolecular reactivities. Thus, the unimolecular isomerization through electrocyclization is the major decomposition path for title molecules. Rational design can prevent thermal isomerization of Ar4-o-QDMs. A new general procedure to generate Ar4-o-QDM has been established here that includes two-electron reduction of the corresponding dications, whose reaction conditions no longer promote electrocyclization of Ar4-o-QDM. Several derivatives of Ar4-o-QDM with the dihydrophenanthrene, dibenzoperylene, or acenaphthene skeleton were isolated for the first time, and the details on their highly strained molecular structures were investigated by low-temperature X-ray analyses. Based on the reversible interconversion between Ar4-o-QDMs and the precursor dications, they represent a new class of electrochromic redox pairs.
This mini review focused briefly on the recent advancement of the synthetically valuable organic transformations catalyzed by polynuclear ruthenium complexes; I) thiolate-bridged diruthenium complex-catalyzed propargylic substitution reaction, and II) N-N double bond cleavage of azobenzene by triruthenium pentahydrido complex.
This short review describes syntheses and properties of several π-conjugated polymers bearing boron atoms in the main chains. These polymers exhibit interesting optical and electronic properties including strong luminescence because of conjugation between π* orbitals of the unsaturated hydrocarbon units and vacant 2p orbitals of the boron atoms. Boron-containing π-conjugate polymers are potentially applicable for novel organic functional materials.
This article describes my memories of studying in the University of Cambridge, Department of Chemistry. I was participated in a project of total synthesis of spongistatin 1 led by Professor Steven V. Ley CBE*1, FRS*2. This article reviews the success of the project, as well as a current relationship between the University of Cambridge and European industries, which may draw attentions of Japanese academic and industrial researchers. *1. Commander of the British Empire. *2. Fellow of the Royal Society.